Impact of antiretroviral therapy (ART) timing on chronic immune activation/inflammation and end-organ damage

Abstract

Purpose of review: The purpose of this review was to summarize recent studies on the effect of early antiretroviral therapy (ART) in HIV-infected patients on markers of immune activation/inflammation, viral persistence and serious non-AIDS events.

Recent findings: Early ART, initiated within days to months of HIV infection, was associated with marked reduction in T-cell activation often reaching levels observed in HIV-uninfected individuals. However, the impact of early ART on markers of innate immune activation, microbial translocation and inflammation/coagulation was less clear. Early ART has also been associated with a significant reduction in the frequency of latently infected cells, which was greater if ART was initiated within days to weeks rather than months following infection. However, few studies have evaluated the relationship between immune activation and viral reservoirs, specifically following early ART. Early ART may potentially reduce serious non-AIDS events and associated mortality, but most of these studies have extrapolated from changes in surrogate markers, such as CD4 : CD8 ratio.

Summary: Early ART was associated with beneficial effects on multiple markers of immune activation, inflammation and viral persistence. Longer term prospective studies are still needed to determine whether early ART translates to a significant reduction in serious non-AIDS events and mortality.

FIGURE 1

Potential mechanisms driving interactions between immune activation and virus persistence on ART. Early ART leads to reduction in activated CD4⁺ T cells, enhanced CD4⁺ T-cell recovery and reduced tissue damage that may potentially contribute to reduced virus persistence on ART. ART, antiretroviral therapy; IL7, interleukin 7; TNF-α, tumor necrosis factor-α.